The mechanism of luteinization in the rhesus monkey and pig will be investigated using cultures of granulosa cells. Once a mechanism is obtained using the in vitro approach it will be confirmed and extended in vivo in the rhesus monkey. A thorough examination of the mechanism involved in production of granulosa cell gonadotropin receptors during follicular maturation will be made. As an extension of this it is hoped to find out more about the nature of LH and FSH receptors using I125-hCG as a marker for the LH receptor. Cyclic 3',5'-AMP levels which are sensitive to LH will also be used as a measure of gonadotropin receptors. Since prostaglandins appear to be involved in LH induced luteinization maybe between the receptor and adenyl cyclase, their role will be examined further by the use of inhibitors of prostaglandin synthesis as well as by the use of prostaglandin antibodies. Since the egg is thought to secrete a luteinization inhibitor into follicular fluid the site of action of this inhibitor will be examined in porcine granulosa cell cultures and suspensions. Attempts will be made to isolate it from ova cultures and follicular fluid. The role of gonadotropins as well as other hormones such as insulin, thyroxin and cortisol in granulosa cell luteinization will be examined in cultures of monkey and porcine granulosa cells grown in chemically defined media. In order to test the physiological significance of the in vitro studies, substances thought to be involved in luteinization will be injected into follicles of the rhesus monkey and their effects on luteinization observed. Control of luteinization in normal and pathological conditions can better be understood once the mechanism of luteinization is known.